Project description
Finding the method in the madness: high resolution studies of unconventional proteins
The growing realisation a couple of decades ago that intrinsically disordered proteins (IDPs) with tremendous conformational flexibility and structural plasticity are widespread and functionally significant, has turned protein science on its head. Mutations of breast cancer susceptibility protein 1 (BRCA1), an IDP, significantly increase the risk of developing hereditary breast or ovarian cancer. However, difficulty studying it due to its disorder has left mastectomy as the only treatment. The EU-funded HYPROTIN project is developing a research platform that will enable studies of BRCA1 with extremely high temporal and spatial resolution. This might open new avenues for rational drug design for many pathologies linked to IDPs.
Objective
HYPROTIN proposes a pioneering research platform for hyperpolarized magnetic resonance of breast-cancer related proteins that will revolutionize our view on tumorigenesis at the atomic level, through bottom-up reconstitution of medicinal relevant interaction pathways involving the breast cancer susceptibility protein 1 (BRCA1).
The risk to develop a hereditary breast or ovarian cancer (HBOC) increases to 55-65 % upon mutation of the BRCA1 gene. Yet, little is known about the biochemistry of tumorigenesis, so that drugs directed towards molecular targets are not satisfactory. To date, mastectomy remains the only preventive treatment. This dramatic lack of knowledge is a consequence of BRCA1 being an intrinsically disordered protein (IDP). Recognizing the importance of IDPs has revolutionized structural biology in the last decade, but this also represents a huge experimental challenge. To date, nuclear magnetic resonance (NMR) is the only technique available to study IDPs at high resolution. However, several limits of the technique must be overcome. Its low sensitivity impedes investigations under biologically meaningful conditions, so that new approaches are required.
The HYPROTIN project aims to achieve two methodological goals: 1) Residue-resolved studies of the BRCA1 IDP under physiological conditions; and 2) real-time monitoring of BRCA1-ligand binding, thereby adding a time-resolved dimension to the NMR characterization of IDPs. This systematic approach will provide unprecedented insight into the BRCA1 interactome, provide medically relevant data and residue-resolved protein interaction kinetics. This will open a new knowledge base for rational drug design.
The project will employ cutting-edge equipment that is unique worldwide, and will represent the first facility in Europe suited for these ground-breaking experiments. The PI has unique interdisciplinary experience enabling the demanding hyperpolarization approach to IDPs.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences clinical medicine oncology breast cancer
- natural sciences biological sciences genetics mutation
- natural sciences physical sciences optics spectroscopy
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
ERC-STG - Starting Grant
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Call for proposal
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(opens in new window) ERC-2018-STG
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1010 Wien
Austria
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